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Premature ovarian insufficiency (POI) is characterized by cessation of menstruation before 40 years of age and elevated serum level of FSH (>25 IU/L). Recent studies have found a few causative genes responsible for POI enriched in meiotic recombination and DNA damage repair pathways.
To investigate the role of variations in homologous recombination genes played in POI pathogenesis.
The whole exome sequencing was performed in 50 POI patients with primary amenorrhea. Functional characterizations of the novel variants were carried out in budding yeast and human cell line.
We identified 8 missense variants in 7 homologous recombination genes, including EXO1, RAD51, RMI1, MSH5, MSH2, MSH6, and MLH1. The mutation p.Thr52Ser in EXO1 impaired the meiotic process of budding yeast and p.Glu68Gly in RAD51-altered protein localization in human cells, both of them impaired the efficiency of homologous recombination repair for DNA double-stranded breaks in human cells.
Our study first linked the variants of EXO1 and RAD51 with POI and further highlighted the role of DNA repair genes in ovarian dysgenesis.
Our study first linked the variants of EXO1 and RAD51 with POI and further highlighted the role of DNA repair genes in ovarian dysgenesis.
The cue reactivity paradigm allows for systematic evaluation of motivational responses to drug-related cues that may elicit drug use. The literature on this topic has grown substantially in recent decades, and the methodology used to study cue reactivity has varied widely across studies. The present research provided a meta-analytic investigation of variables that have an impact on cue reactivity effects to enhance our understanding of this key feature of tobacco use disorders.
A total of 128 publications yielded 249 effect sizes, which were analyzed to investigate the magnitude of the cue reactivity effect and potential moderators.
Craving generated a moderate-to-large effect size (Hedges' g = 0.71, p < .001), indicating that drug cues produced significantly greater craving than neutral cues. However, physiological variables yielded significantly lower or nonsignificant effect sizes. Analyses of a variety of empirically and theoretically relevant moderator variables showed that cue modality, cue perst 20 years, a time of rapid growth for this literature. The study leads to a better understanding of the cue reactivity paradigm across different self-report and physiological variables and identifies factors that may modulate addictive motivation for tobacco cigarettes.
A core feature of addiction is that drug-related cues can have a major impact on motivational responses across multiple substance use disorders, including tobacco cigarettes. This paper describes a meta-analysis updating and synthesizing cue reactivity research with tobacco cigarette smokers over the last 20 years, a time of rapid growth for this literature. The study leads to a better understanding of the cue reactivity paradigm across different self-report and physiological variables and identifies factors that may modulate addictive motivation for tobacco cigarettes.
Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear.
Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT.
Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96±11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07±2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12to8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol.
Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.
Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.
To measure US hospitals' adoption of electronic health record (EHR) functions that support care for older adults, focusing on structured documentation of the 4Ms (What Matters, Medication, Mentation, and Mobility) and electronic health information exchange/communication with patients, caregivers, and long-term care providers.
In an online survey of a national, random sample of 797 US acute-care hospitals in 2018-2019, 479 (60.1%) responded. We calculated nationally representative measures of the percentages of hospitals with EHRs that include structured documentation of the 4Ms and exchange/communications functions.
Structured EHR documentation of the 4Ms was fully implemented in at least 1 unit in 64.0% of hospitals and across all units in 41.5% of hospitals. Of the 4Ms, structured documentation was the highest for medications (91.3% in at least 1 unit) and the lowest for mentation (70.3% in at least 1 unit). All exchange/communication functions had been implemented in at least 1 unit in 16.2% of facilities and across all units in 7.6% of hospitals. TRC051384 solubility dmso Less than half of the hospitals had an EHR portal for long-term care facilities to access hospital information (45.4% in at least 1 unit), sent information electronically to long-term care facilities (44.6%), and had training for adults/caregivers on the patient portal (32.1%).
Despite significant national investment in EHRs, hospital EHRs do not yet include key documentation, exchange, and communication functions needed to support evidence-based care for the older adults who comprise the majority of the inpatient population. Additional policy efforts are likely needed to promote the expansion of EHR capabilities into these high-value domains.
US acute-care hospital EHRs are lacking key functions that support care for older adults.
US acute-care hospital EHRs are lacking key functions that support care for older adults.
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